JP2024081237A - Automated analyzer and mass sensor - Google Patents

Abstract

[Problem] A predetermined amount of specimen and sample is accurately dispensed to ensure the reliability of analysis results. [Solution] This automatic analyzer includes a reagent holder that holds a reagent container that stores a reagent, a specimen holder that holds a specimen container that stores a specimen, a dispensing mechanism that dispenses the reagent and the specimen into a reaction vessel, and a mass sensor that measures the mass of the reaction vessel. The mass sensor includes a fixing part, a vibration plate at least a portion of which is fixed to the fixing part, a piezoelectric element bonded to the vibration plate, and a vessel installation part that is supported by the vibration plate and is configured to be able to install the reaction vessel into which the liquid to be measured is discharged. [Selected Figure] Figure 1

Description

The present invention relates to an automatic analyzer and a mass sensor.

Quantitative measurements of the concentrations of chemical substances, such as proteins, lipids, sugars, ions, and the various components that make up these substances, contained in body fluids such as blood and urine are performed in clinical practice. Automated analyzers are known as devices that automate the processes required for these measurements (e.g., quantitative separation of specimen samples, mixing with reagents, determining reaction results, measuring changes in substances contained in the reagents, etc.).

Automated analyzers perform analysis of the components of samples by reacting a specified amount of sample and reagent in a reaction vessel and measuring the absorbance and luminescence of the sample. The device is equipped with a dispensing mechanism for dispensing the sample and reagent into the reaction vessel. The dispensing mechanism is required to be configured to dispense a specified amount of sample and reagent.

In an automated analyzer, the mass of liquid dispensed in one dispensing operation is small, about 4 to 60 mg. This makes it difficult to accurately measure the mass of the dispensed liquid. If some kind of abnormality occurs in the dispensing mechanism and analysis is performed without obtaining the specified amount of dispensed liquid, the correct analysis results will not be obtained.

Furthermore, because automatic analyzers have a dispensing mechanism, various motors, and moving parts, there is a problem of frequent disturbance due to vibration. In order to measure the exact mass of dispensed specimens and reagents without being subjected to disturbance vibration, it is possible to install a vibration isolation table or the like and place an electronic balance or the like on the vibration isolation table. However, since vibration isolation tables are large, providing an automatic analyzer with a vibration isolation table would result in an increase in the size of the automatic analyzer, which is not realistic. In view of this situation, there is a demand for an automatic analyzer and mass sensor that can accurately dispense specimens and samples to ensure the reliability of analysis results.

JP 2010-217048 A

The present invention provides an automatic analyzer and a mass sensor that can accurately dispense a predetermined amount of specimen or sample to ensure the reliability of the analysis results.

The automated analyzer according to the present invention includes a reagent holder that holds a reagent container that stores a reagent, a specimen holder that holds a specimen container that stores a specimen, a dispensing mechanism that dispenses the reagent and the specimen into a reaction vessel, and a mass sensor that measures the mass of the reaction vessel. The mass sensor includes a fixing section, a vibration plate at least a portion of which is fixed to the fixing section, a piezoelectric element bonded to the vibration plate, and a vessel installation section that is supported by the vibration plate and is configured to be capable of installing the reaction vessel into which the liquid to be measured is discharged.

The mass sensor according to the present invention is a mass sensor that measures the mass of a liquid dispensed into a reaction vessel, and is characterized by comprising a fixing part, a vibration plate at least a portion of which is fixed to the fixing part, a piezoelectric element bonded to the vibration plate, and a vessel installation part that is supported by the vibration plate and is configured to be capable of installing a reaction vessel into which a reagent and a sample are dispensed.

The present invention provides an automatic analyzer and mass sensor that can accurately dispense a predetermined amount of specimen or sample to ensure the reliability of the analysis results.

1 is an overall schematic diagram of an automatic analyzer 1 according to a first embodiment. FIG. 2 is a perspective view showing the details of the configuration of the mass sensor 2. 4 is a graph illustrating the operation of the mass sensor 2. 4 is a flowchart illustrating the operation of the automatic analyzer 1 according to the first embodiment. 10 is a flowchart illustrating the operation of an automatic analyzer 1 according to a second embodiment.

Hereinafter, the present embodiment will be described with reference to the attached drawings. In the attached drawings, functionally identical elements may be indicated by the same or corresponding numbers. Note that the attached drawings show embodiments and implementation examples according to the principles of the present disclosure, but these are for understanding the present disclosure and are in no way used to interpret the present disclosure in a restrictive manner. The descriptions in this specification are merely typical examples and do not limit the scope or application examples of the present disclosure in any sense.

In this embodiment, the disclosure is described in sufficient detail for a person skilled in the art to implement the disclosure, but it should be understood that other implementations and forms are possible, and that changes to the configuration and structure and substitutions of various elements are possible without departing from the scope and spirit of the technical ideas of the disclosure. Therefore, the following description should not be interpreted as being limited to this.

[First embodiment]
The overall configuration of an automatic analyzer 1 according to a first embodiment will be described with reference to Fig. 1. The automatic analyzer 1 is roughly composed of a reagent disk (reagent holder) 102, a specimen disk (specimen holder) 104, an incubator 106, a reaction vessel tray 107, a gripper 108, a detection unit 109, a reaction vessel disposal port 110, a dispensing mechanism 111, a mass sensor 2, and a washing tank 117, as an example.

The reagent disk 102 is a reagent holding section that holds a reagent container 101 that contains a reagent to be used in analysis. The specimen disk 104 is a specimen holding section that holds a specimen container 103 that contains a specimen to be tested. The reagent disk 102 and the specimen disk 104 are configured to be movable (for example, rotatable around a rotation axis) by moving mechanisms 102a and 104a, respectively. By moving the reagent disk 102 and the specimen disk 104, the dispensing mechanism 111 can access the reagent container 101 and the specimen container 103 and aspirate the reagent and specimen (liquid). After aspirating, the dispensing mechanism 111 can access the reaction container 105 arranged at the ejection position 112 of the mass sensor 2 and eject the aspirated liquid.

The incubator 106 has a function of promoting the reaction of the reaction vessels 105, which have been injected with reagents and samples, in an environment where the temperature is controlled to a constant temperature. The reaction vessel tray 107 holds unused reaction vessels 105. The gripper 108 has a function of gripping the reaction vessels 105 and transporting them to the mass sensor 2, the detection unit 109, the reaction vessel disposal port 110, etc. The detection unit 109 receives the reaction vessels 105 that have undergone a predetermined reaction time in the incubator 106 and performs analysis of the sample. The reaction vessel disposal port 110 constitutes a disposal section for disposing of the used reaction vessels 105 after the analysis is completed. The washing tank 117 can wash the dispensing mechanism 111. Washing can prevent components from being carried over when dispensing different liquids.

The mass sensor 2 is a measurement unit that measures the mass of the liquid discharged into the reaction vessel 105 disposed at the discharge position 112. FIG. 2 is a perspective view showing the details of the configuration of the mass sensor 2. As an example, the mass sensor 2 is configured to include a piezoelectric element 202, a vibration plate 203, a fixing unit 204, a vessel installation unit 205, and a control unit 206.

As shown in FIG. 2, the piezoelectric element 202 can be bonded to one or both sides of the vibration plate 203, which is formed in a circular plate shape as an example, at a position concentric with the vibration plate 203. The piezoelectric element 202 is polarized in the thickness direction, and when an AC voltage is applied to the electrodes formed on both sides, the expansion and contraction of the piezoelectric element 202 can generate a bending vibration in the vibration plate 203 with the center position of the disk as the antinode. The vibration plate 203 can be made of a metal material such as aluminum or titanium.

The fixing part 204 constitutes the base part of the mass sensor 2, and has an upper fixing member and a lower fixing member as shown in FIG. 2, for example, and the upper and lower fixing members sandwich the outer peripheral part of the diaphragm 203 from above and below, thereby making it possible to fix the diaphragm 203. In other words, the diaphragm 203 is configured to obtain vibration with the fixing part 204 as the fixed end. The outer peripheral part of the diaphragm 203 does not need to be fixed to the fixing part 204 along the entire circumference, and it is sufficient that at least a portion of it is fixed as long as vibration of the diaphragm 203 can be obtained.

The container mounting section 205 is configured to be able to mount the reaction container 105, and specifically, has a housing section capable of housing the reaction container 105 therein, and is fixed to approximately the center of the vibration plate 203. In other words, the container mounting section 205 is installed approximately in the center of a flexural vibrator formed by bonding the piezoelectric element 202 and the vibration plate 203 together. The container mounting section 205 is installed on the vibration plate 203 so that it can vibrate together with the flexural vibration of the vibration plate 203. It is preferable that the container mounting section 205 is fixed to a position where the vibration amplitude of the vibration plate 203 is approximately maximum when an AC voltage of a predetermined frequency is applied to the piezoelectric element 202.

A control unit 206 is connected to the electrodes of the piezoelectric element 202. The control unit 206 functions as a power supply unit that supplies AC voltage to the piezoelectric element 202, and also constitutes a detection unit that detects the resonance frequency f of the resonance unit 207 composed of the piezoelectric element 202, the vibration plate 203, the container installation unit 205, and the reaction container 105, and a mass calculation unit that calculates the mass of the reaction container 105 based on the detected resonance frequency. By detecting the absolute value |Δf| of the amount of change in the resonance frequency before and after dispensing, the change in mass Δm before and after dispensing, i.e., the mass of the dispensed liquid, can be measured (see FIG. 3).

When the resonating part 207 vibrates near the resonant frequency of a specific vibration mode, the vibration system can be approximated as a one-degree-of-freedom spring/mass damper system. In this case, the resonant frequency fr at which the vibration velocity v becomes maximum when a harmonic excitation force F is applied to the vibration system is expressed by the following [Equation 1]. Here, k and m are the equivalent spring constant and equivalent mass of the vibration system, respectively.

When liquid is dispensed into the reaction vessel 105 and the mass of the vibration system changes by Δm (dispensed mass), the change Δf in the resonance frequency fr is expressed by Equation 2 when the dispensed mass Δm is sufficiently small compared to the mass m of the entire vibration system. Since the difference Δf in the resonance frequency before and after dispensing is proportional to the dispensed mass Δm, the dispensed mass Δm can be calculated based on the change Δf. The reaction vessel 105 has a variation in mass due to manufacturing variation. The mass variation of the reaction vessel 105 is too large compared to the dispensed mass to be ignored. By using the difference Δf in the resonance frequency before and after dispensing, the effect of the mass variation of the reaction vessel 105 can be reduced and the dispensed mass Δm can be calculated.

The resonant frequency fr used by the mass sensor 2 to measure the dispensed amount is preferably 1 kHz or higher to avoid the effects of disturbance vibrations caused by the operation of the automatic analyzer 1, and is preferably 6 kHz or lower, which is the primary natural frequency of the reaction vessel 105, as a frequency at which deformation of the reaction vessel 105 can be ignored. By making the vibration plate 203 and the piezoelectric element 202 into a disk shape and using flexural vibration with the outer periphery of the vibration plate 203 fixed, it is possible to achieve a resonant frequency of 1 kHz to 6 kHz in a small, lightweight configuration that can be mounted on an automatic analyzer.

The reaction vessel 105 is installed (mounted) in the vessel installation section 205 by the gripper 108, and is removed (detached) from the vessel installation section 205. When the reaction vessel 105 is attached or detached, an external force much larger than the load due to the dispensed mass is applied to the mass sensor 2. By supporting the outer periphery of the vibration plate 203 with the fixing section 204, the load due to the attachment or detachment of the reaction vessel 105 is distributed to the entire outer periphery, which has the effect of preventing the vibration plate 203 and the piezoelectric element from being damaged by the external force.

As described above, when the specified amount of liquid is not dispensed to the reaction vessel 105 at the dispensing position 112 due to an abnormal operation of the dispensing mechanism 111, the mass sensor 2 can detect an abnormality in the dispensed amount. Specifically, the control unit 206 can determine whether the dispensed amount is normal or not based on the result of a comparison between the default dispensed amount and the dispensed amount calculated by the control unit 206.

The operation of measuring the mass of liquid dispensed into the reaction vessel 105 in the automatic analyzer 1 of the first embodiment will be described with reference to the flowchart in FIG. 4. When automatic analysis is performed by the automatic analyzer 1, first, an empty reaction vessel 105 is placed in the vessel placement section 205 of the mass sensor 2 (step S301). Then, with the empty reaction vessel 105 placed, the resonant frequency f1 is measured in the mass sensor 2 (step S302).

Then, the specimen and reagent (liquid) are discharged into the reaction vessel 105 (step S303), and then the resonant frequency f2 of the reaction vessel 105 after the discharge is measured by the mass sensor 2 (step S304). Then, based on the measured resonant frequencies f1 and f2, the mass (Δm) of the liquid discharged in step S303 is calculated (step S305). If the difference between the calculated mass and the default discharge amount exceeds a threshold value, the control unit 206 determines that the discharge amount is abnormal, and can notify the operator by displaying this fact on a display (not shown) or the like.

In this way, the automated analyzer 1 of the first embodiment calculates the mass of the liquid dispensed into the reaction vessel 105 based on the first resonance frequency of the resonance unit before the liquid is dispensed into the reaction vessel and the second resonance frequency of the resonance unit after the liquid is dispensed. The mass sensor 2 includes a fixed part 204, a vibration plate 203 at least a part of which is fixed to the fixed part 204, a piezoelectric element 202 bonded to the vibration plate 203, and a vessel installation part 205 supported by the vibration plate 203 and configured to be able to install the reaction vessel 105. The resonance frequency f of the resonance part 207 composed of the piezoelectric element 202, the vibration plate 203, the vessel installation part 205, and the reaction vessel 105 changes depending on the mass of the liquid dispensed into the reaction vessel 105, so the control part 206 can detect the mass of the dispensed liquid and detect an abnormality by detecting this change in the resonance frequency f. With this configuration, even if there is manufacturing variation in the reaction vessel 105, it is possible to accurately measure the mass of the dispensed liquid without being affected by it.

As described above, the automated analyzer 1 and mass sensor 2 of the first embodiment can accurately dispense a predetermined amount of specimen and sample, ensuring the reliability of the analysis results.

[Second embodiment]
Next, an automatic analyzer according to a second embodiment will be described with reference to Fig. 5. The automatic analyzer 1 according to the second embodiment may have the same overall configuration as that of the first embodiment (Fig. 1), and the structure of the mass sensor 2 may also be the same (Fig. 2). However, the automatic analyzer 1 according to the second embodiment is different from the first embodiment in the operation of measuring the mass of the liquid dispensed into the reaction vessel 105. Specifically, in the automatic analyzer 1 according to the second embodiment, the liquid (sample and reagent) is discharged into one reaction vessel 105 multiple times, and it is determined whether the discharged mass of the liquid for each discharge operation is normal.

The operation of measuring the mass of liquid dispensed into the reaction vessel 105 in the automated analyzer 1 of the second embodiment will be described with reference to the flowchart in FIG. 5. Steps S401 to S405 are the same as steps S301 to S305 in the first embodiment, so duplicated explanations will be omitted here.

In step S406, if some of the multiple discharge operations into one reaction vessel 105 mounted on the mass sensor 2 have not been completed and liquid to be discharged remains (NO), the process proceeds to step S407, where the resonance frequency f2 in the previous measurement is replaced with f1 (i.e., the resonance frequency f2 after the discharge operation in the previous discharge/mass measurement is set to the resonance frequency f1 before the discharge operation in the next measurement).

Next, in step S403, a new liquid is ejected into the reaction vessel 105, and the resonant frequency f2 after the ejection is measured again (step S404). Then, based on the resonant frequency f1 (before the new ejection operation) set in step S407 and the newly obtained resonant frequency f2, the ejection mass of the liquid in the new ejection operation is calculated (step S405). The above is repeated until the specified number of ejection operations is completed.

As described above, in the second embodiment of the automated analyzer 1, the dispensing operation into one reaction vessel 105 is performed multiple times, and the dispensing mass for each of the multiple dispensing operations is measured by the mass sensor 2. Therefore, according to the second embodiment, in addition to obtaining the same effect as the first embodiment, each of the multiple dispensing operations is managed, so that the dispensing operations can be managed more accurately.

Although the embodiments of the present invention have been described above, these embodiments are presented as examples and are not intended to limit the scope of the invention. These novel embodiments can be embodied in various other forms, and various omissions, substitutions, and modifications can be made without departing from the gist of the invention. These embodiments and their modifications are included in the scope and gist of the invention, and are included in the scope of the invention and its equivalents as set forth in the claims.

1...automatic analyzer 2...mass sensor 101...reagent container 102...reagent disk 103...specimen container 104...specimen disk 105...reaction container 106...incubator 107...reaction container tray 108...gripper 109...detection unit 110...reaction container disposal port 111...dispensing mechanism 112...discharge position 117...washing tank 201...discharge liquid 202...piezoelectric element 203...vibration plate 204...fixing section 205...container installation section 206...control section 207...resonation section

Claims (12)

a reagent container for storing a reagent;
a specimen holder for holding a specimen container for storing a specimen;
a dispensing mechanism that dispenses the reagent and the sample into a reaction vessel;
a mass sensor for measuring a mass of the reaction vessel;
The mass sensor includes:
A fixed portion;
A diaphragm at least a portion of which is fixed to the fixing portion;
A piezoelectric element bonded to the vibration plate;
a container installation section configured to be capable of installing the reaction container supported by the vibration plate and into which a liquid to be measured is discharged. a resonance unit is configured by the diaphragm, the container installation unit, and the reaction container,
a first resonant frequency of the resonator before the liquid is dispensed into the reaction vessel;
2. The automatic analyzer according to claim 1, further comprising a step of calculating a mass of the liquid dispensed into the reaction vessel based on a second resonant frequency of the resonating section at a time point after the liquid is dispensed into the reaction vessel. the dispensing mechanism executes a plurality of dispensing operations for one of the reaction vessels, and the mass sensor measures a mass of the reaction vessel for each of the dispensing operations;
3. The automated analyzer according to claim 2, wherein the mass sensor sets the previous second resonant frequency to the first resonant frequency for each of the plurality of ejection operations, and sets the resonant frequency measured after a new ejection operation to the second resonant frequency. The diaphragm is disk-shaped,
The automated analyzer according to claim 1 , wherein the fixing portion fixes at least a portion of an outer periphery of the diaphragm. 5. The automatic analyzer according to claim 1, wherein the container mounting portion is fixed to approximately the center of the vibration plate. The automatic analyzer of any one of claims 1 to 4, characterized in that the container mounting portion is fixed at a position where the vibration amplitude of the vibration plate is approximately maximum when an AC voltage of a predetermined frequency is applied to the piezoelectric element. A mass sensor for measuring a mass of a liquid discharged into a reaction vessel,
A fixed portion;
A diaphragm at least a portion of which is fixed to the fixing portion;
A piezoelectric element bonded to the vibration plate;
a container installation section supported by the vibration plate and configured to be capable of installing a reaction container into which a reagent and a sample are discharged. a resonance section is formed by the diaphragm, the container installation section, and the reaction container,
a first resonant frequency of the resonator before the liquid is dispensed into the reaction vessel;
8. The mass sensor according to claim 7, wherein a mass of the liquid dispensed into the reaction vessel is calculated based on a second resonance frequency of the resonating portion at a time point after the liquid is dispensed into the reaction vessel. the dispensing mechanism executes a plurality of dispensing operations for one of the reaction vessels, and the mass sensor measures a mass of the reaction vessel for each of the dispensing operations;
9. The mass sensor according to claim 8, wherein, for each ejection operation among the plurality of ejection operations, the mass sensor sets the previous second resonant frequency to the first resonant frequency, and sets the resonant frequency measured after a new ejection operation to the second resonant frequency. The diaphragm is disk-shaped,
The mass sensor according to claim 7 , wherein the fixing portion fixes at least a part of an outer periphery of the diaphragm. The mass sensor according to any one of claims 7 to 10, wherein the container installation portion is fixed to approximately the center of the vibration plate. The mass sensor according to any one of claims 7 to 10, characterized in that the container installation portion is fixed at a position where the vibration amplitude of the vibration plate is approximately maximum when an AC voltage of a predetermined frequency is applied to the piezoelectric element.

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